      Document 0158
 DOCN  DRG0158
 UNIQUE IDENTIFIER        DRG-0089
 NAME OF SUBSTANCE        Smallpox vaccine [USAN 1996]
 SYNONYMS                 Dryvax [AHFS Drug Information 1995]
 PROTOCOL ID NUMBERS      FDA 063A
 SECONDARY SOURCE ID      AI452-003001 [FDA 63A]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Used to promote active
                          immunity to smallpox in individuals exposed
                          to the disease or virus.  The vaccine
                          contains vaccinia virus which is
                          antigenically similar to variola virus, the
                          causative agent of smallpox.  Administration
                          of vaccinia virus promotes the production of
                          specific antibodies which confer immunity
                          against smallpox. Following administration of
                          vaccine, local replication of vaccinia virus
                          occurs; replication of the vaccinia virus may
                          occur in the regional lymph nodes.
                          Protection that results from immunization is
                          probably the result of both T and B
                          cell-mediated antibodies.  Following primary
                          immunization, antibody appears in the serum
                          within 4-5 days, peaks within 4 weeks, and
                          persists for several years. The skin response
                          to immunization appears within 3-5 days,
                          peaks within 4 weeks, and may show evidence
                          of change for up to 20 years following
                          immunization.  Appearance of antibody in
                          serum without a skin response occurs rarely
                          following primary immunization; however,
                          absence of a skin response usually indicates
                          an inadequate immune response to the vaccine.
                          Immunization is highly protective, although
                          the exact mechanism of protection has not
                          been fully established. Nearly 100% of the
                          individuals who receive vaccine are protected
                          during the first 1-3 years following
                          immunization.  The duration of immunity has
                          not been definitely established, but the
                          vaccine generally provides substantial but
                          waning immunity for 10 years or more.
                          Individuals exposed to smallpox who were
                          immunized more than 3 years before exposure
                          may develop smallpox; however, the disease
                          process is generally modified and nonfatal.
                          This modification of disease following
                          exposure may occur up to 20 years following
                          immunization. [AHFS Drug Information 1995]
 DISEASES STUDIED/TREATED Control in vaccine studies [FDA 063A]
 DISEASES STUDIED/TREATED Comparative study of HIVAC-le and the
                          smallpox vaccine in previously vaccinated and
                          unvaccinated volunteers [FDA 063A]
 CLASSIFICATION CODE      Vaccine [AHFS Drug Information 1995]
 OTHER MAJOR USES         Used only to promote active immunity to
                          smallpox in individuals exposed to the
                          disease or virus (e.g., laboratory workers
                          directly involved with smallpox or closely
                          related orthopox viruses and civilians
                          producing or testing smallpox vaccine) [AHFS
                          Drug Information 1995]
 SUBSTANCE INTERACTIONS   In general, individuals receiving
                          immunosuppressive therapy (e.g.
                          corticotropin, corticosteroids, alkylating
                          agents, antimetabolites, radiation therapy)
                          may have a diminished response to smallpox
                          vaccine and replication of the virus may be
                          potentiated. [AHFS Drug Information 1990].
                          Concomitant smallpox vaccination and
                          dexamethasone therapy and concomitant
                          smallpox vaccination and prednisone therapy
                          have been reported to result in
                          immunosuppression produced by corticosteroids
                          and impairment of the response to smallpox
                          vaccine, increasing the risk of generalized
                          vaccinia. Concomitant indomethacin and
                          smallpox vaccination has been reported to
                          alter the response to smallpox vaccination.
                          Concomitant methotrexate and smallpox
                          vaccination has been reported to impair the
                          immunologic response to smallpox vaccine and
                          result in generalized vaccinia. [AHFS Drug
                          Information 1995] [Drug Interactions 3rd ed,
                          1975] [Drug Interaction 4th ed., 1979]
 ADVERSE EFFECTS          Primary immunization results in a typical
                          skin response at the site of administration
                          with swelling and tenderness, some regional
                          lymphadenopathy and occasionally a low grade
                          fever.  Generalized vaccinia, manifested as
                          an erythematous urticarial rash, frequently
                          occurs 7-12 days following administration of
                          the vaccine.  The rash is self-limiting and
                          usually persists for a few days; individuals
                          are not acutely ill.  Eczema vaccinatum may
                          occur as a result of local spread and/or
                          dissemination of vaccinia virus infections in
                          individuals with a previous history of atopic
                          dermatitis or eczema.  Bullous erythema
                          multiforme occurs rarely.  Vaccinia necrosum,
                          characterized by progressive necrosis of an
                          apparently normal skin response to the
                          vaccine has been reported rarely.  Fever,
                          headache and meningeal signs occur 1-2 weeks
                          after immunization and may be followed by
                          ataxia, muscular weakness, paralysis,
                          lethargy, coma, and seizures; permanent brain
                          damage may result.  Secondary bacterial
                          infections may occur at the vaccination site.
                           Other adverse effects reported include
                          myocarditis, thrombocytopenia, arthritis,
                          pericarditis, lymphangitis, lymphadenitis,
                          osteomyelitis and pneumonia.  Adverse nervous
                          system effects including encephalitis,
                          encephalomyelitis, encephalopathy, transverse
                          myelitis, neuromyelitis optica and acute
                          infectious polyneuritis have occurred rarely
                          following administration of smallpox vaccine.
                           Malignant melanoma has developed rarely in
                          the vaccination scar at the administration
                          site.  Acute erythema nodosum leprosum or
                          lepra reactions have been reported following
                          administration of smallpox vaccine to
                          individuals with lepromatous leprosy. [AHFS
                          Drug Information 1995]
 CONTRAINDICATIONS        Primary and booster immunizations with
                          smallpox vaccine are generally
                          contraindicated in infants with failure to
                          thrive, premature infants, and small, weak
                          debilitated children; individuals of any age
                          with eczema, wounds, burns, poison ivy,
                          impetigo, or other chronic form of dermatitis
                          as well as siblings or other household
                          contacts of these individuals; individuals
                          with leukemia, lymphomas of any other type,
                          or other malignant neoplasms affecting the
                          bone marrow or lymphatic systems; individuals
                          with known or suspected disorders of gamma
                          globulin synthesis (e.g.
                          dysgammaglobulinemia); and individuals
                          receiving immunosuppressive therapy (e.g.
                          corticotropin, corticosteroids, radiation
                          therapy, certain antineoplastic agents).
                          However, the manufacturer states that there
                          are no absolute contraindications to the use
                          of smallpox vaccine in direct contacts of
                          patients with smallpox or in endemic areas.
                          Vaccine should probably be administered with
                          caution to those who have exhibited previous
                          systemic allergic reactions to smallpox
                          vaccine or any ingredient in the formulation
                          (e.g. polymyxin B, dihydrostreptomycin,
                          chlortetracycline tracycline, neomycin).  The
                          risk of severe adverse reactions appears to
                          be greatest in children younger than 1 year
                          of age. Administration of smallpox vaccine to
                          pregnant women during weeks 3-24 of gestation
                          may cause fetal vaccinia which usually
                          results in fetal death. [AHFS Drug
                          Information 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Lyophilized preparation of
                          live vaccinia virus prepared from calf lymph
                          and grown in the skin of a vaccinated bovine
                          calf [AHFS Drug Information 1995]
 CHEMICAL/PHYSICAL DATA   STABILITY: Stable for 10 days at room
                          temperature.  Under refrigeration, the
                          product has a shelf life of 18 months; after
                          reconstitution, the vaccine may be stored for
                          3 months refrigerated [AHFS Drug Information
                          1995]
 CHEMICAL/PHYSICAL DATA   STABILITY: Trace amounts of antibiotics added
                          during manufacturing to eliminate bacterial
                          contamination may be present in the final
                          reconstituted vaccine [AHFS Drug Information
                          1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: The lyophilized vaccine
                          occurs as a yellow to grayish pellet which
                          may become fragmented upon shaking [AHFS Drug
                          Information 1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Lyophilized powder for
                          reconstitution and diluent [AHFS Drug
                          Information 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Administered intradermally
                          by the multiple pressure technique,
                          preferably over the deltoid region of the
                          arm. [AHFS Drug Information 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Lyophilized smallpox vaccine should
                          be refrigerated at 2-8 C. [AHFS Drug
                          Information 1995]
 MANUFACTURERS            Wyeth-Ayerst
 REFERENCES               Slade HB. HIV immunotherapy [letter]
                          [published erratum appears in Vaccine 1994
                          Aug;12(11):1055]. Vaccine. 1994
                          Apr;12(5):476.
 REFERENCES               Hart JF. Smallpox and AIDS [letter; comment].
                          Can Med Assoc J. 1994 Aug 1;151(3):271.
 REFERENCES               Tartaglia J, Cox WI, Taylor J, Perkus M,
                          Riviere M, Meignier B, Paoletti E. Highly
                          attenuated poxvirus vectors. AIDS Res Hum
                          Retroviruses. 1992 Aug;8(8):1445-7.
 REFERENCES               Graham BS, Belshe R, Clements ML, Dolin R,
                          Fernie B, Stablein D, Wright P, Koff W.
                          HIV-GP160 recombinant vaccinia vaccination of
                          vaccinia-naive adults followed by RGP160
                          booster immunization. Int Conf AIDS. 1991 Jun
                          16-21;7(2):88 (abstract no. F.A.1).
 REFERENCES               Baxby D. Smallpox. Int J STD AIDS. 1991;2
                          Suppl 1:8-12.
 REFERENCES               Graham B, Belshe R, Midthun K, Dolin R,
                          Fernie B, Stablein D, Wright P, Koff W. HIV
                          gp160 recombinant vaccinia in vaccinia-naive
                          adults. Int Conf AIDS. 1990 Jun
                          20-23;6(2):346 (abstract no. 1131).
 REFERENCES               Keefer MC, Bonnez W, Roberts NJ Jr, Lambert
                          J, Dolin R, Reichman R. HIV-1 rgp160-specific
                          cellular immune responses by recipients of a
                          live vaccinia-rgp160 vaccine. Int Conf AIDS.
                          1990 Jun 20-23;6(2):326 (abstract no. 1051).
 ENTRY MONTH              9007
 LAST REVISION DATE       960208
 

SOURCE: National Library of Medicine, Bethesda, MD.  Distributed by AEGIS.
